The Polarity Protein Pals1 Regulates Radial Sorting of Axons

Zollinger, Daniel R.; Chang, Kae-Jiun; Baalman, Kelli; Kim, Seonhee; Rasband, Matthew N.

doi:10.1523/jneurosci.1593-15.2015

Cited by 21 publications

(22 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epithelial-like cell polarization is essential during Schwann cell myelination and in particular in the control of the geometric parameters evident in the mature myelin sheath ( Masaki, 2012 ). The first evidence of the role of polarity proteins during SC myelination was established in pre/early myelinating cells whereby Pals1, Par3, and LKB1 facilitates the polarization of E-cadherin and p75 receptor in the glial membrane, directly adjacent to the axon ( Chan et al, 2006 ; Shen et al, 2014 ; Zollinger et al, 2015 ). This first polarization step is critical to initiate the myelin sheath wrapping of the axon.…”

Section: Epithelial-like Polarization and Geometry Of The Myelin Sheamentioning

confidence: 99%

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

Tricaud

2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Myelin sheath geometry, encompassing myelin sheath thickness relative to internodal length, is critical to optimize nerve conduction velocity and these parameters are carefully adjusted by the myelinating cells in mammals. In the central nervous system these adjustments could regulate neuronal activities while in the peripheral nervous system they lead to the optimization and the reliability of the nerve conduction velocity. However, the physiological and cellular mechanisms that underlie myelin sheath geometry regulation are not yet fully elucidated. In peripheral nerves the myelinating Schwann cell uses several molecular mechanisms to reach and maintain the correct myelin sheath geometry, such that myelin sheath thickness and internodal length are regulated independently. One of these mechanisms is the epithelial-like cell polarization process that occurs during the early phases of the myelin biogenesis. Epithelial cell polarization factors are known to control cell size and morphology in invertebrates and mammals making these processes critical in the organogenesis. Correlative data indicate that internodal length is regulated by postnatal body growth that elongates peripheral nerves in mammals. In addition, the mechanical stretching of peripheral nerves in adult animals shows that myelin sheath length can be increased by mechanical cues. Recent results describe the important role of YAP/TAZ co-transcription factors during Schwann cell myelination and their functions have linked to the mechanotransduction through the HIPPO pathway and the epithelial polarity factor Crb3. In this review the molecular mechanisms that govern mechanically-driven myelin sheath elongation and how a Schwann cell can modulate internodal myelin sheath length, independent of internodal thickness, will be discussed regarding these recent data. In addition, the potential relevance of these mechanosensitive mechanisms in peripheral pathologies will be highlighted.

show abstract

Section: Epithelial-like Polarization and Geometry Of The Myelin Sheamentioning

confidence: 99%

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

Tricaud

2018

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In the second report, Shen et al found that regardless of any metabolic functions, LKB1 deletion in SCs compromises the proper localization of the critical cell polarity protein Par‐3, which has been previously proposed to be important for myelination in an in vitro co‐culture system . However, given that the in vivo functions of Par‐3 and other polarity components in SCs are likely redundant, it is conceivable that abnormal localization of Par‐3 may have arisen because of the metabolic abnormalities in crippled SCs, and Par‐3 inactivation, per se , does not contribute to the dysmyelination observed. In this respect, it would be important in the future to characterize nerve development and myelination in conditional mutants lacking Par‐3 in SCs.…”

Section: Perinatal Lkb1 Disruption In Scs Impairs Myelinationmentioning

confidence: 99%

The LKB1‐AMPK and mTORC1 Metabolic Signaling Networks in Schwann Cells Control Axon Integrity and Myelination

Beirowski

2018

BioEssays

View full text Add to dashboard Cite

The Liver kinase B1 with its downstream target AMP activated protein kinase (LKB1-AMPK), and the key nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) form two signaling systems that coordinate metabolic and cellular activity with changes in the environment in order to preserve homeostasis. For example, nutritional fluctuations rapidly feed back on these signaling systems and thereby affect cell-specific functions. Recent studies have started to reveal important roles of these strategic metabolic regulators in Schwann cells for the trophic support and myelination of axons. Because aberrant intermediate metabolism along with mitochondrial dysfunction in Schwann cells is mechanistically linked to nerve abnormalities found in acquired and inherited peripheral neuropathies, manipulation of the LKB1-AMPK, and mTORC1 signaling hubs may be a worthwhile therapeutic target to mitigate nerve damage in disease. Here, recent advances in our understanding of LKB1-AMPK and mTORC1 functions in Schwann cells are covered, and future research areas for this key metabolic signaling network are proposed.

show abstract

“…Thus, Pals1 transiently colocalizes with Par‐3 at the adaxonal Schwann cell membrane then in the paranodes and clefts (Ozcelik et al, ; Poliak et al, ; Zollinger, Chang, Baalman, Kim, & Rasband, ) where they form a biochemical complex (Zollinger, Chang, et al, ). Knockout/knockdown studies indicate Pals1 is required for the timely onset of Schwann cell myelination and the fidelity of radial sorting of axons (Ozcelik et al, ; Zollinger, Chang, et al, ). Future studies to determine whether Necl‐4 recruits the full Par‐3 polarity complex to the adaxonal membrane as well as other components of the Crumbs complex, in addition to Pals1, will be of considerable interest.…”

Section: Discussionmentioning

confidence: 99%

Necl‐4/Cadm4 recruits Par‐3 to the Schwann cell adaxonal membrane

Meng

Maurel

Lam

et al. 2018

Glia

View full text Add to dashboard Cite

Interactions between axons and Schwann cells are essential for the acquisition of Schwann cell radial and longitudinal polarity and myelin sheath assembly. In the internode, the largest of these longitudinal domains, axon-Schwann cell interactions are mediated by the Nectin-like (Necl) cell adhesion proteins, also known as SynCAMs or Cadms. In particular, Necl-1/Cadm3 expressed on the axon surface binds to Necl-4/Cadm4 expressed along the adaxonal membrane of myelinating Schwann cells. Necl-4 promotes myelination in vitro and is required for the timely onset of myelination and the fidelity of the organization of the myelin sheath and the internode in vivo. A key question is the identity of the downstream effectors of Necl-4 that mediate its effects. The cytoplasmic terminal region (CTR) of Necl-4 contains a PDZ-domain binding motif. Accordingly, we used the CTR of Necl-4 in an unbiased proteomic screen of PDZ-domain proteins. We identify Par-3, a multi-PDZ domain containing protein of the Par-aPKC polarity complex previously implicated in myelination, as an interacting protein. Necl-4 and Par-3 are colocalized along the inner Schwann cell membrane and coprecipitate from Schwann cell lysates. The CTR of Necl-4 binds to the first PDZ domain of Par-3 thereby recruiting Par-3 to sites of Necl-4/Necl-1 interaction. Knockdown of Necl-4 perturbs Par-3 localization to the inner membrane of Schwann cells in myelinating co-cultures. These findings implicate interactions of Necl-1/Necl-4 in the recruitment of Par-3 to the Schwann cell adaxonal membrane and the establishment of Schwann cell radial polarity. K E Y W O R D S axon, cell adhesion, myelin, polarity, Schwann cell

show abstract

The Polarity Protein Pals1 Regulates Radial Sorting of Axons

Cited by 21 publications

References 45 publications

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath Elongation

The LKB1‐AMPK and mTORC1 Metabolic Signaling Networks in Schwann Cells Control Axon Integrity and Myelination

Necl‐4/Cadm4 recruits Par‐3 to the Schwann cell adaxonal membrane

Contact Info

Product

Resources

About